lncRNA Biomarkers of Glioblastoma Multiforme.

Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14-16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients' blood.

Biomolecules to Biomarkers? U87MG Marker Evaluation on the Path towards Glioblastoma Multiforme Pathogenesis.

The heterogeneity of the glioma subtype glioblastoma multiforme (GBM) challenges effective neuropathological treatment. The reliance on in vitro studies and xenografted animal models to simulate human GBM has proven ineffective. Currently, a dearth of knowledge exists regarding the applicability of cell line biomolecules to the realm of GBM pathogenesis. Our study's objectives were to address this preclinical issue and assess prominin-1, ICAM-1, PARTICLE and GAS5 as potential GBM diagnostic targets. The methodologies included haemoxylin and eosin staining, immunofluorescence, in situ hybridization and quantitative PCR. The findings identified that morphology correlates with malignancy in GBM patient pathology. Immunofluorescence confocal microscopy revealed prominin-1 in pseudo-palisades adjacent to necrotic foci in both animal and human GBM. Evidence is presented for an ICAM-1 association with degenerating vasculature. Significantly elevated nuclear PARTICLE expression from in situ hybridization and quantitative PCR reflected its role as a tumor activator. GAS5 identified within necrotic GBM validated this potential prognostic biomolecule with extended survival. Here we present evidence for the stem cell marker prominin-1 and the chemotherapeutic target ICAM-1 in a glioma animal model and GBM pathology sections from patients that elicited alternative responses to adjuvant chemotherapy. This foremost study introduces the long non-coding RNA PARTICLE into the context of human GBM pathogenesis while substantiating the role of GAS5 as a tumor suppressor. The validation of GBM biomarkers from cellular models contributes to the advancement towards superior detection, therapeutic responders and the ultimate attainment of promising prognoses for this currently incurable brain cancer.

The role of abdominal ultrasonography in patients with isoattenuating pancreatic carcinoma.

AIMS: The main objective of this study was to determine the sensitivity of abdominal ultrasonography (US) in patients with isoattenuating pancreatic carcinoma and to compare the frequency of secondary signs on abdominal US and endoscopic ultrasonography (EUS) in these tumours. METHODS: Twenty-four patients with histologically or cytologically verified isoattenuating pancreatic carcinoma who underwent abdominal US, contrast-enhanced CT and EUS of the pancreas as part of the diagnostic workup were included in this retrospective study. The sensitivity of abdominal US in detecting the isoattenuating pancreatic carcinoma was investigated and the frequency of secondary signs of isoattenuating pancreatic carcinoma on abdominal US and EUS was compared. RESULTS: In 5 of 24 patients (21%) with isoattenuating pancreatic carcinoma, a hypoechogenic pancreatic lesion was directly visualised on abdominal US. Secondary signs were present on US in 21 patients (88%). These included dilatation of the common bile duct and/or intrahepatic bile ducts in 19/24 (79%), dilatation of the pancreatic duct in 3/24 (13%), abnormal contour/inhomogeneity of the pancreas in 1/24 (4%), and atrophy of the distal parenchyma in 1/24 (4%). Pancreatic duct dilatation was observed more frequently on EUS than on abdominal US (P=0.002). For other secondary signs, there was no significant difference in their detection on abdominal US and EUS (P=0.61-1.00). CONCLUSION: Abdominal US is capable of detecting secondary signs of isoattenuating pancreatic carcinoma with high sensitivity and has the potential to directly visualise these tumours.

All-Trans Retinoic Acid Fosters the Multifarious U87MG Cell Line as a Model of Glioblastoma.

Glioblastoma multiforme (GBM) is a primary brain cancer of poor prognosis, with existing treatments remaining essentially palliative. Current GBM therapy fails due to rapid reappearance of the heterogeneous neoplasm, with models suggesting that the recurrent growth is from treatment-resistant glioblastoma stem-like cells (GSCs). Whether GSCs depend on survival/proliferative cues from their surrounding microenvironmental niche, particularly surrounding the leading edge after treatment remains unknown. Simulating human GBM in the laboratory relies on representative cell lines and xenograft models for translational medicine. Due to U87MG source discrepancy and differential proliferation responses to retinoic acid treatment, this study highlights the challenges faced by laboratory scientists working with this representative GBM cell line. Investigating the response to all trans-retinoic acid (ATRA) revealed its sequestering of the prominin-1 stem cell marker. ICAM-1 universally present throughout U87MG was enhanced by ATRA, of interest for chemotherapy targeting studies. ATRA triggered diverse expression patterns of long non-coding RNAs PARTICLE and GAS5 in the leading edge and established monolayer growth zone microenvironment. Karyotyping confirmed the female origin of U87MG sourced from Europe. Passaging U87MG revealed the presence of chromosomal anomalies reflective of structural genomic alterations in this glioblastoma cell line. All evidence considered, this study exposes further phenotypic nuances of U87MG which may belie researchers seeking data contributing towards the elusive cure for GBM.

Improvement of the Diagnosis of Isoattenuating Pancreatic Carcinomas by Defining their Characteristics on Contrast Enhanced Computed Tomography and Endosonography with Fine-Needle Aspiration (EUS-FNA).

(1) Background. The aim was to define typical features of isoattenuating pancreatic carcinomas on computed tomography (CT) and endosonography and determine the yield of fine-needle aspiration endosonography (EUS-FNA) in their diagnosis. (2) Methods. One hundred and seventy-three patients with pancreatic carcinomas underwent multiphase contrast-enhanced CT followed by EUS-FNA at the time of diagnosis. Secondary signs on CT, size and location on EUS, and the yield of EUS-FNA in isoattenuating and hypoattenuating pancreatic cancer, were evaluated. (3) Results. Isoattenuating pancreatic carcinomas occurred in 12.1% of patients. Secondary signs of isoattenuating pancreatic carcinomas on CT were present in 95.2% cases and included dilatation of the pancreatic duct and/or the common bile duct (85.7%), interruption of the pancreatic duct (76.2%), abnormal pancreatic contour (33.3%), and atrophy of the distal parenchyma (9.5%) Compared to hypoattenuating pancreatic carcinomas, isoattenuating carcinomas were more often localized in the pancreatic head (100% vs. 59.2%; p < 0.001). In ROC (receiver operating characteristic) analysis, the optimal cut-off value for the size of isoattenuating carcinomas on EUS was ≤ 25 mm (AUC = 0.898). The sensitivity of EUS-FNA in confirmation of isoattenuating and hypoattenuating pancreatic cancer were 90.5% and 92.8% (p = 0.886). (4) Conclusions. Isoattenuating pancreatic head carcinoma can be revealed by indirect signs on CT and confirmed with high sensitivity by EUS-FNA.

Estimating the radiation dose to the fetus during prophylactic internal iliac occlusion in patients with abnormal placentation.

AIMS: To evaluate the estimated fetal radiation dose during prophylactic internal iliac arterial occlusion in patients with abnormal placenta and to estimate the risk of radiation induced cancer in child age. METHODS: Prophylactic occlusion of the internal iliac arteries during Caesarean section was performed in 42 patients with placenta praevia and/or placenta accreta spectrum. Fogarty embolectomy catheters were used for prophylactic occlusion of the internal iliac arteries. All procedures were performed in the hybrid operating room using Philips Allura Xper FD 20 X-ray system. Low dose X-ray fluoroscopy (7.5 frames per second) was used. The CODE (Conceptus dose estimation) Software was used to estimate the fetal dose and the risk of radiation induced carcinoma. RESULTS: Fluoroscopy times required for insertion of Fogarty catheters were 0.5-4.2 min (mean: 1.7 min, median: 1.5 min). The estimated radiation dose to the fetus was 0.26-3.36 mGy (mean: 1.49 mGy, median: 1.25 mGy). The risk of radiation induced cancer in child age was 0.01-0.04% (mean 0.02%, median 0.01%). One patient developed thrombosis of a common femoral artery. CONCLUSION: Prophylactic occlusion of the internal iliac arteries is a simple and safe procedure with minimal risk of complications and with a very low estimated radiation dose to the fetus.

Unpacking Pandora From Its Box: Deciphering the Molecular Basis of the SARS-CoV-2 Coronavirus.

An enigmatic localized pneumonia escalated into a worldwide COVID-19 pandemic from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This review aims to consolidate the extensive biological minutiae of SARS-CoV-2 which requires decipherment. Having one of the largest RNA viral genomes, the single strand contains the genes ORF1ab, S, E, M, N and ten open reading frames. Highlighting unique features such as stem-loop formation, slippery frameshifting sequences and ribosomal mimicry, SARS-CoV-2 represents a formidable cellular invader. Hijacking the hosts translational engine, it produces two polyprotein repositories (pp1a and pp1ab), armed with self-cleavage capacity for production of sixteen non-structural proteins. Novel glycosylation sites on the spike trimer reveal unique SARS-CoV-2 features for shielding and cellular internalization. Affording complexity for superior fitness and camouflage, SARS-CoV-2 challenges diagnosis and vaccine vigilance. This review serves the scientific community seeking in-depth molecular details when designing drugs to curb transmission of this biological armament.

Impact of blood pressure levels within first 24 hours after mechanical thrombectomy on clinical outcome in acute ischemic stroke patients.

INTRODUCTION: Despite early management and technical success of mechanical thrombectomy (MT) for acute ischemic stroke (AIS), not all patients reach a good clinical outcome. Different factors may have an impact and we aimed to evaluate blood pressure (BP) levels in the first 24 hours after MT. METHODS: Consecutive AIS patients treated with MT were enrolled in the retrospective bi-center study. Neurological deficit was assessed with National Institutes of Health Stroke Scale (NIHSS) and functional outcome after 3 months with modified Rankin scale (mRS) with a score 0-2 for good outcome. The presence of symptomatic intracerebral hemorrhage (SICH) was assessed according to the SITS-MOST criteria. RESULTS: Of 703 treated patients, completed BP levels were collected in 690 patients (350 males, mean age 71±13 years) with median of admission NIHSS 17 points. Patients with mRS 0-2 had a lower median of systolic BP (SBP) compared with those with poor outcome (131 vs 140 mm Hg, P<0.0001). The rate of SICH did not differ between the patients with a median of SBP <140 mm Hg and ≥140 mm Hg. (5.1% vs 5.1%, P=0.980). Multivariate regression analysis with adjustment for potential confounders showed a median of distolic BP (P=0.024, OR: 0.977, 95% CI: 0.957 to 0.997) as a predictor of good functional outcome after MT, and a median of maximal SBP (P=0.038; OR: 0.990, 95% CI: 0.981 to 0.999) in the patients with achieved recanalization. CONCLUSION: Lowering of BP within the first 24 hours after MT may have a positive impact on clinical outcome in treated patients.

ECG non-gated multi-detector computed tomography protocol prior to catheter ablation of atrial fibrillation provides sufficient data quality with lower radiation exposure compared to ECG-gated protocol - results of a prospective, randomized and blinded study.

BACKGROUND: The role of ECG-gating in left atrium (LA) computed tomography (MDCT) imaging is not precisely defined. METHODS AND RESULTS: 62 patients were randomized according to ECG gating with prospective evaluation of image quality, Volume CT Dose Index, Dose Length Product, Effective Dose and registration error between anatomical map and MDCT. We found significant difference in all radiation variables, but not in visual quality, registration error, CA duration, CA fluoroscopy time and CA fluoroscopy dose. CONCLUSION: Helical non-gated MDCT achieved a radiation dose more than four times lower with comparable image quality and course of ablation compared to ECG-gated protocol.

Surgical revision vs. stent-graft to treat venous anastomosis stenosis following surgical thrombectomy of hemodialysis grafts.

BACKGROUND: There is no unanimous strategy for treating stenosis of the venous anastomosis (VA) of an occluded arteriovenous graft (AVG) following surgical thrombectomy. In this study, we compared classical surgical treatment and endovascular treatment procedures with the use of stent- graft in a single center study. The aim was to evaluate whether, the VA stenosis of thrombosed AVG treated endovascularly by stent-graft implantation, have as good results as surgical VA treatment, so that it may be considered the method of choice. METHODS: The study included patients who underwent surgical AVG thrombectomy with subsequent angiographically confirmed VA stenosis between 1/2009 and 12/2014. Surgical angioplasty was then performed in 15 patients and 17 patients underwent primary stent-graft implantation. RESULTS: In the surgically treated patients, the postintervention primary patency, primary assisted patency and secondary patency after 12 months were 50.7%, 56.3%, 62.4%, respectively. In the group of patients with occluded AVG who underwent stent-graft implantation, the postintervention primary patency, primary assisted patency and secondary patency after 12 months were 32.8%, 44.1% a 55.6%, respectively. No statistically significant difference in primary patency (P=0.391), primary assisted patency (P=0.605), and secondary patency (P=0.702) was observed between the groups. CONCLUSIONS: Stent-graft implantation into stenotic VA of an occluded AVG showed to be effective and maintained good long-term patency. It is the preferred method due to its minimal invasiveness. The superiority of this method must be confirmed on a larger set of patients.

Late Rupture of Lumbar Artery as an Unusual Complication after Renal Biopsy - Case Report.

The most serious complication of renal biopsy is vascular damage with subsequent haemorrhage. To our knowledge, we present a first ever case of lumbar artery (LA) rupture accompanied by massive retroperitoneal bleeding, which developed after a significant amount of time following the biopsy itself. In a 63-year-old Caucasian female patient, a percutaneous left kidney biopsy was performed under continuous ultrasound guidance. On the fourteenth day after the procedure, she was examined for a sudden onset of left lumbar region pain. Computed tomography angiography showed a large retroperitoneal hematoma with active bleeding from the fourth left LA. Successful endovascular superselective embolization was performed immediately. The predisposing factor for the late haemorrhage could have been anticoagulation therapy, renal insufficiency and older age. Our case report highlights the need for caution, especially when performing kidney biopsy in a group of high-risk patients, particularly if they are indicated for subsequent anticoagulant therapy.

"Sun Ray" Appearance in a Case of Cardiac Angiosarcoma: A Comparison of MRI and PET/CT.

Our article reports a case of a 35-year-old man with cardiac mass, who underwent a wide range of imaging methods, including cardiac magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT). Contrast-enhanced MRI images revealed "sun ray" pattern in the mass. Final histopathological diagnosis of angiosarcoma was confirmed during autopsy. To our knowledge, our case is the second direct observation of this MRI diagnostic pattern and the first one that allows a comparison with PET/CT findings.

Current treatment methods for long occlusions of the femoropopliteal segment in patients with intermittent claudication: Minireview.

UNLABELLED: Backround. Intermittent claudication is a classic symptom of peripheral arterial disease. It is mainly treated conservatively but if this fails, a form of revascularization is indicated. The revascularization in chronic occlusion of femoropopliteal region is currently performed by two basic methods: the standard method of surgical bypass and the newer miniinvasive alternative represented by the endovascular method. The treatment of patients with solely claudication and long occlusion of femoropopliteal region remains controversial. The aim of this minireview was to determine whether surgical bypass is still the best method of choice in a time of endovascular techniques. METHODS: A MEDLINE search for original and review articles using key terms, intermittent claudication and long femoropopliteal oclusion. RESULTS AND CONCLUSION: No ideal treatment for long occlusions of the femoropopliteal segment has been established to date. It is clear that the role of endovascular techniques in the treatment of SFA occlusions is increasing. It remains that, lower risk patients with claudication should be examined to assess the quality of veins suitable for revascularization and bypass should be selected as the first method of choice.

The HLA-Cw*06 allele and -1149 G/T polymorphism of extrapituitary promoter of PRL gene as a possible common genetic predisposing factors to psoriasis vulgaris and psoriatic arthritis in Czech population.

Psoriatic arthritis (PsA) affects approximately 30 % of patients suffering from psoriasis vulgaris (PsV), but the risk factors for its development have not been well elucidated yet. The HLA-Cw*06 allele was described as a predisposing factor to PsV. Prolactin is known as an immune response modulator, and its elevated levels present risk for PsV development. It is possible that these factors interact and together emphasize the predisposition to both diseases. We tested on an association of HLA-Cw alleles and functional polymorphism -1149 G/T in PRL gene extrapituitary promoter with PsV and PsA in Czech population. We found a statistically significant association between HLA-Cw*06 allele and PsV (P corrected = 0.0013) that was most prominent in early onset disease subtype (P corrected = 0.0013). The association between HLA-Cw*06 and PsA was low (P corrected = 0.0585) and restricted to PsA patients with early PsV onset (P corrected = 0.0195). We found no association of -1149 G/T PRL gene polymorphism with either PsV or PsA.

Cystic adventitial disease of the popliteal artery: report on three cases and review of the literature.

BACKGROUND: During the past nine years three cases of cystic adventitial disease of the popliteal artery have been diagnosed and treated in our medical institution. Different approaches were used in the treatment in all these cases. The purpose of this report is to summarise the current knowledge of the etiology, presentation, diagnostics and treatment of this condition, with the addition of new cases. METHODS: Information about three new cases is presented and discussed together with that from the relevant publications obtained from the Pubmed database. Results. In the first case resection with synthetic graft interposition was used. Nine years after the surgery the patient is without any signs of recurrence, but he experienced local thrombolysis of the occluded graft and repeated PTA of hemodynamically significant anastomotic stenoses. The second case treated with US-guided aspiration has demanded repeated reinterventions due to recurrence; nevertheless, the result is satisfactory. In the last instance, the cyst was evacuated and excised. Six months after the surgery the patient is symptom-free and without signs of recurrence. CONCLUSIONS: CAD of the popliteal artery is a rare vascular condition. However, it must be considered in the differential diagnosis, especially in middle-aged male patients without evidence of atherosclerotic disease in whom intermittent claudication has developed suddenly with a rapid progression or with fluctuation in severity. Duplex ultrasound and MRA are the the best diagnostic methods. Based on the existing knowledge, the treatment of choice is surgery (either evacuation with the removal of the cystic wall or resection and grafting).

Chromosomal damage in peripheral blood lymphocytes of newly diagnosed cancer patients and healthy controls.

BACKGROUND: The majority of human cancers arise from cells unable to maintain genomic stability. Recent prospective studies indicated that enhanced chromosomal aberrations (CAs) frequencies are predictive of gastrointestinal and lung cancers. However, studies on incident cancer patients are lacking; thus, we investigated chromosomal damage in newly diagnosed cancer patients and healthy individuals. METHODS: We analyzed chromosomal damage in peripheral blood lymphocytes in a group of 300 incident cancer patients (with different malignancies) in comparison with 300 healthy controls. RESULTS AND CONCLUSIONS: The frequencies of aberrant cells (ACs) and CAs were significantly higher in patients (2.38 +/- 1.56 and 2.53 +/- 1.69, respectively) as compared with controls (1.81 +/- 1.31 and 1.94 +/- 1.47, respectively, P < 0.01). The percentual difference in chromatid-type aberrations (CTAs) between patients and controls was moderately significant (1.37 +/- 1.20 and 1.11 +/- 0.99, respectively, P

Is the biliary manometric perfusion test effective in the evaluation of balloon dilatation treatment success of benign biliary strictures?

BACKGROUND: The success of balloon dilatation treatment of benign biliary strictures (BBS) is usually evaluated by 'clinical test'. For objective evaluation of treatment success, measurement of the pressure inside the biliary tree after treatment has been proposed. AIM: The aim of this article is to assess the role of biliary manometric perfusion test (BMPT) in the evaluation of treatment success of BBS and to assess the long term biliary patency after evaluation by BMPT. MATERIALS AND METHODS: From February 2003 to January 2008, 12 patients (median age 53.5 years) after balloon dilatation treatment were evaluated by BMPT. BMPT was done after a mean of 3 dilatations over a mean period of 6.85 months. An intrabiliary pressure less than 20 cm of water during the test was considered as success threshold. RESULTS: The pressures during BMPT were less than 20 cm of water in 11 out of 12 patients. Subsequently the drain was removed and patients were followed up clinically. Two patients on follow-up required re-intervention 13 days and 11 months later. The remaining 9 patients had no evidence of biliary obstruction at a mean following of 15.3 months. Using the statistical Kaplan-Meier analysis, the probability of biliary patency up to 9 months was 90.9% and at 1, 2 and 3 years was 77%. CONCLUSION: BMPT is effective in the evaluation of treatment success of BBS. It is simple, cost effective, gives immediate results and helps us to determine the treatment end point.

Endotension after endovascular treatment of abdominal aortic aneurysm: percutaneous treatment.

Endotension is one of the possible specific late complications of endovascular treatment of abdominal aortic aneurysm (AAA). We describe the treatment of endotension in a small group of 3 patients (all men, aged 58, 70, and 70-years-old) by translumbar puncture of the aneurysm sac and aspiration of its content. It was transudate and its culture was negative. Sac size reduced after aspiration in all patients and no subsequent enlargement was seen. Percutaneous translumbar puncture of the aneurysm sac with aspiration of sac content could be an easy and effective method of treatment in endotension. But a larger group of patients and long-term follow-up are needed.

HLA-Cw*06 class I region rather than MICA is associated with psoriatic arthritis in Czech population.

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease which affects patients suffering from psoriasis. The genetic background especially the susceptibility loci on the short arm of the chromosome six contribute to PsA development. In our study, we looked for the role of the MICA and HLA-Cw genes polymorphisms in PsA pathogenesis. We investigated 100 PsA patients and 94 healthy Czech individuals. We found an association between HLA-Cw*06 and PsA namely PsA with psoriasis type I (age of psoriasis onset before 40 years) compared to healthy individuals (P (corrected) < 0.05, OR 2.56, CI 95% 1.33-4.76 and P (corrected) = 0.01, OR 3.03, CI 95% 1.53-5.88, respectively). The MICA-A9 allele of the transmembrane microsatelite MICA polymorphism occurred more frequently in PsA with psoriasis type II group (age of psoriasis onset after 40 years) than in controls, 58.6 versus 38.0%, respectively however, this finding did not reach a statistical significance after correction (P (corrected) = 0.085).

Endovascular treatment of abdominal aortic paraanastomotic pseudoaneurysms after surgical reconstruction.

PURPOSE: To evaluate the efficacy of endovascular treatment of paraaortic postoperative abdominal aortic pseudoaneurysms. MATERIALS AND METHODS: From April 1996 to November 2007 five men with paraaortic postoperative abdominal aortic pseudoaneurysm underwent endovascular treatment. Average age was 64.2 years (range 54-73). The average time interval between the primary surgery and endovascular treatment was 12.4 years (4 months-23 years). Three patients were treated by aortouniiliacal stentgrafts and two patients by tube stentgrafts. RESULTS: Technical success rate was 100%. Pseudoaneurysms were primarily excluded from circulation without perioperative complications in all patients. At follow-up (mean 38.5 months) there were no deaths and no endoleaks. In one patient thrombosis of stentgraft was found and it was successfully treated by thrombectomy. All pseudoaneurysms still continued to be excluded from circulation in the last follow-up. CONCLUSION: Endovascular treatment is minimally invasive, effective and safe option of surgery for paraaortic postoperative pseudoaneurysms.